Our purpose is to study the analytical and clinical toxicology of acute drug overdose, which usually follows suicide attempts, in order to improve clinical laboratory diagnosis and support, and increase knowledge of plasma drug levels and drug distribution following drug overdose. This includes improvement of procedures which are suitable for around the clock emergency use, as well as the development of more sensitive, specific procedures to determine the concentrations of parent drug and metabolite following overdose; the latter data also will be used for clinical correlation studies. Previously we described a procedure for the emergency analysis of the drugs most commonly involved in overdose. We developed and tested on clinical specimens a computer program for processing the analytical data which reduces the need for specialized knowledge by the technologist. We also published studies of the clinical correlation of plasma levels of chlordiazepoxide, methyprylon and methaqualone. Our emergency procedures rely on UV spectrophotometry which is ideally suited to emergency toxicology. More sensitive and specific procedures including gas chromatography with selective (nitrogen) detectors and mass fragmentography will be developed to determine concentrations of parent drug following overdose with various benzodiazpines and results compared with those determined by our emergency UV methods. The more sensitive (GLC-nitrogen detector) procedures will be used to study overdose concentrations of drugs which achieve relatively low levels (tricyclics, chlorpromazine). The methods developed, and knowledge obtained studying overdose, should also be of value to those involved in clinical pharmacologic studies of therapeutic levels. BIBLIOGRAPHIC REFERENCES: Jatlow, P., Application of gas chromatography - mass spectrometry to the rapid routine measurement of anticonvulsants in the clinical laboratory, (abstract), proceedings of Pittsburgh Conference on Anal. Chem., 1976. Jatlow, P. Analytical toxicology in the clinical laboratory - an overview. Laboratory Medicine (editorial), 11-15, 1976.